Interaction of PrP with NRAGE, a protein involved in neuronal apoptosis.
Prion diseases involve the conversion of the endogenous prion protein, PrP(C), into a disease-associated form PrP(Sc). Reports show that a subset of PrP(C) is subject to degradation in the cytosol by the ubiquitin-proteasome system. Some studies show that cytosolic PrP(C) is neuroprotective, while others show that it is neurotoxic. Here, ... we report that cytosolic PrP(C) constructs interact with a pro-apoptotic protein, NRAGE (neurotrophin receptor interacting MAGE homolog). This novel interaction was identified in a yeast two-hybrid screen using PrP(C) as bait and confirmed by an in vitro binding assay and co-immunoprecipitations. Endogenous NRAGE accumulated in perinuclear aggregates following proteasome inhibition, and recombinant NRAGE and PrP(C)-EGFP co-localized in aggresomes after proteasome inhibition. Finally, co-expression of NRAGE and cytosolic PrP(C) affected mitochondrial membrane potential in neuroblastoma cells. Our results suggest that interaction of cytosolic PrP and NRAGE could affect neuronal viability.
Mesh Terms:
Animals, Apoptosis, Brain, COS Cells, Cell Survival, Cercopithecus aethiops, Disease Models, Animal, Female, Inclusion Bodies, Macromolecular Substances, Membrane Potentials, Mice, Mice, Inbred BALB C, Mitochondria, Neoplasm Proteins, Nerve Degeneration, PC12 Cells, PrPC Proteins, Prion Diseases, Proteasome Endopeptidase Complex, Rats
Animals, Apoptosis, Brain, COS Cells, Cell Survival, Cercopithecus aethiops, Disease Models, Animal, Female, Inclusion Bodies, Macromolecular Substances, Membrane Potentials, Mice, Mice, Inbred BALB C, Mitochondria, Neoplasm Proteins, Nerve Degeneration, PC12 Cells, PrPC Proteins, Prion Diseases, Proteasome Endopeptidase Complex, Rats
Mol. Cell. Neurosci.
Date: Jun. 01, 2005
PubMed ID: 15911347
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